Damen Layla, Grootjen Lionne N, Donze Stephany H, Juriaans Alicia F, de Graaff Laura C G, van der Velden Janielle A E M, Hokken-Koelega Anita C S
Dutch Growth Research Foundation, Rotterdam, The Netherlands.
Department of Pediatrics, Subdivision of Endocrinology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
Clin Endocrinol (Oxf). 2020 Oct;93(4):439-448. doi: 10.1111/cen.14274. Epub 2020 Jul 22.
Growth hormone (GH) has been approved for children with Prader-Willi syndrome (PWS) and significantly improves body composition in adults with PWS. Adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2). Continuation of GH maintains body composition, but GH is known to induce insulin resistance, which might affect glucose homeostasis. Studies on long-term effects of GH treatment in adults are very limited.
To investigate effects of 3 years of GH treatment on glucose homeostasis and prevalence of metabolic syndrome (MS) in adults with PWS.
Open-label, prospective study.
43 young adults with PWS.
Dutch PWS Reference Center.
Glucose and insulin during oral glucose tolerance test.
Estimated mean (95% CI) fasting glucose and insulin levels remained stable during 3 years of GH treatment. Glucose being 4.6 (4.4-4.8) mmol/l at start and 4.7 (4.6-4.9) mmol/l after 3 years (P = .07); insulin being 59.5 (45.2-75.8) pmol/l and 56.7 (45.2-69.6) pmol/l resp. (P = .72). Sex, ethnicity and fat mass percentage were significantly associated with fasting glucose levels, while IGF-I or GH-dose were not. Blood pressure, lipids and prevalence of MS remained stable during 3 years of GH. IGT prevalence was variable over time, six patients had IGT at start and eleven after 3 years of GH. One patient developed DMT2. However, prevalence of IGT or DMT2 was not significantly higher after 3 years than at study start.
Three years of GH treatment in adults with PWS does not impair glucose homeostasis and does not lead to an increased prevalence of DMT2.
生长激素(GH)已被批准用于普拉德-威利综合征(PWS)儿童,并且能显著改善PWS成人患者的身体组成。PWS成人患者易发生糖耐量受损(IGT)和2型糖尿病(DMT2)。继续使用GH可维持身体组成,但已知GH会诱导胰岛素抵抗,这可能影响葡萄糖稳态。关于GH治疗对成人长期影响的研究非常有限。
研究3年GH治疗对PWS成人患者葡萄糖稳态及代谢综合征(MS)患病率的影响。
开放标签的前瞻性研究。
43例年轻的PWS成人患者。
荷兰PWS参考中心。
口服葡萄糖耐量试验期间的血糖和胰岛素水平。
在3年的GH治疗期间,估计的平均(95%CI)空腹血糖和胰岛素水平保持稳定。开始时血糖为4.6(4.4 - 4.8)mmol/L,3年后为4.7(4.6 - 4.9)mmol/L(P = 0.07);胰岛素分别为59.5(45.2 - 75.8)pmol/L和56.7(45.2 - 69.6)pmol/L(P = 0.72)。性别、种族和脂肪质量百分比与空腹血糖水平显著相关,而IGF-I或GH剂量则不然。在3年的GH治疗期间,血压、血脂和MS患病率保持稳定。IGT患病率随时间变化,6例患者开始时患有IGT,3年GH治疗后有11例。1例患者发生了DMT2。然而,3年后IGT或DMT2的患病率并不比研究开始时显著更高。
对PWS成人患者进行3年的GH治疗不会损害葡萄糖稳态,也不会导致DMT2患病率增加。